丙氨酸氨基转移酶(ALT)水平健康范围的定义：2021 年更新

StephenW

丙氨酸氨基转移酶水平健康范围的定义：2021 年更新卢卡·瓦伦蒂、塞雷娜·佩鲁西、克里斯蒂安娜·比安科、费鲁乔·切里奥蒂、亚历山德拉·贝尔祖尼、劳拉·伊奥尼亚·普拉特、罗伯塔·特罗蒂、弗朗切斯科·马尔维斯蒂蒂、罗伯塔·丹布罗西奥、皮特罗·兰佩蒂科、阿戈斯蒂诺·科利、马西莫·科伦坡、伊曼纽尔·A. Tsochatquellis、米雷拉·普拉蒂… 少见作者首次发布：2021 年 9 月 14 日https://doi.org/10.1002/hep4.1794地平线 2020 框架计划 (101016726 REVEAL 和 777377 LITMUS)、意大利水稻协会 (16888)、意大利卫生部 (CV PREVITAL “Strategie di prevenzione primaria n”) 和 “Ricerca”-60146Finalizzata 的支持, Associazione Italiana per la Prevenzione dell'Epatite Virale (COPEV) 和 IRCCS Ca' Granda Ospedale Maggiore Policlinico（“Ricerca Corrente”和“'Liver Bible' PR-0361”）。潜在的利益冲突：Prati 博士为 Macopharma 提供建议并获得资助。他获得了 Terumo、Ortho Diagnostics、Grifols、Immucor、Diamed 和 Diatech 的资助。 Lampertico 博士为 Bristol Myers Squibb、Roche、Gilead、GlaxoSmithKline、MSD、AbbVie、Arrowhead、Alnylam、Eigar、Myr Pharma 和 Janssen 提供建议并担任发言人。部分PDFPDF工具分享抽象的肝病流行病学的变化以及推荐的分析方法的修改要求重新评估丙氨酸氨基转移酶 (ALT) 水平的参考上限 (URL)。使用 20 年前整合的相同方法来定义健康人群，我们为新推荐的国际临床化学联合会 (IFCC) 标准化测试定义了 URL。在一项横断面研究中，我们检查了 21,296 名明显健康的献血者（18-65 岁），并通过第 95 个百分位数计算了无肝病危险因素的个体的性别特异性 URL。在一个由 745 名代谢障碍参与者组成的子集、一个由 977 名未经选择的供体组成的独立队列以及 899 名患有慢性肝病的患者中，对这些进行了预测肝损伤的能力。 ALT 水平通过 IFCC 测试测量。男性、体重指数、血糖、血脂、铁蛋白、高血压和年轻是独立的 ALT 预测因子（P < 0.001）。男性/女性的更新 URL 为 42/30 U/L，比 IFCC 当前推荐的 URL 低约 30%。由于灵敏度提高，他们赋予了检测代谢障碍个体脂肪变性和显着纤维化的能力（优势比 [OR] = 2.31，范围 1.40-3.80，P = 0.001；OR = 3.35，范围 1.19-9.42，P = 0.021 ; 分别），尽管准确性有限，并且未选择的供体出现显着纤维化（OR = 2.32, 1.02-5.31, P = 0.045）。更新后的 URL 在区分肝脏状况方面具有中到高的准确度（接收者操作特征曲线下的面积 = 0.81，范围 0.78-0.91）。结论：通过 IFCC 方法更新的 URL 低于初始研究中计算的 URL，但高于使用推荐的旧非标准化方法使用的 URL，并且能够更好地预测肝脏疾病。对仍在使用的不同技术的有限认识应被视为医疗错误的可能来源。缩写ALT    丙氨酸氨基转移酶 AUROC曲线下面积BMI体重指数CI    置信区间乙肝表面抗原    乙肝表面抗原 HCV    丙型肝炎病毒 IFCC    国际临床化学与检验医学联合会LR    似然比LSM    肝脏硬度测量 M/L    男/女 NAFLD脂肪肝    非酒精性脂肪肝 OR    优势比URL    参考上限

StephenW

Definition of Healthy Ranges for Alanine Aminotransferase Levels: A 2021 Update
Luca Valenti, Serena Pelusi, Cristiana Bianco, Ferruccio Ceriotti, Alessandra Berzuini, Laura Iogna Prat, Roberta Trotti, Francesco Malvestiti, Roberta D’Ambrosio, Pietro Lampertico, Agostino Colli, Massimo Colombo, Emmanuel A. Tsochatzis, Mirella Fraquelli, Daniele Prati, … See fewer authors
First published: 14 September 2021
https://doi.org/10.1002/hep4.1794

Supported by Horizon 2020 Framework Programme (101016726 REVEAL and 777377 LITMUS), Associazione Italiana per la Ricerca sul Cancro (16888), Italian Ministry of Health (CV PREVITAL “Strategie di prevenzione primaria n” and “Ricerca Finalizzata RF-2016-02364358”), Associazione Italiana per la Prevenzione dell’Epatite Virale (COPEV), and IRCCS Ca’ Granda Ospedale Maggiore Policlinico (“Ricerca Corrente” and “‘Liver Bible’ PR-0361”).

Potential conflict of interest: Dr. Prati advises and received grants from Macopharma. He received grants from Terumo, Ortho Diagnostics, Grifols, Immucor, Diamed, and Diatech. Dr. Lampertico advises and is on the speakers’ bureau for Bristol Myers Squibb, Roche, Gilead, GlaxoSmithKline, MSD, AbbVie, Arrowhead, Alnylam, Eigar, Myr Pharma, and Janssen.
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Abstract

The changing epidemiology of liver disease, and modifications in the recommended analytical methodology call for a re-evaluation of the upper reference limits (URLs) of alanine aminotransferase (ALT) levels. Using the same approach consolidated 20 years ago to define the healthy population, we defined the URL for the newly recommended International Federation of Clinical Chemistry (IFCC) standardized test. In a cross-sectional study, we examined 21,296 apparently healthy blood donors (age 18-65 years) and calculated the sex-specific URL by the 95th percentile in individuals without risk factors for liver disease. These were tested for the ability to predict liver damage in a subset of 745 participants with dysmetabolism, in an independent cohort of 977 unselected donors, and in 899 patients with chronic liver disease. ALT levels were measured by the IFCC test. Male sex, body mass index, glucose, lipids, ferritin, hypertension, and younger age were independent ALT predictors (P < 0.001). Updated URLs were identified at 42/30 U/L in males/females, approximately 30% lower than those currently recommended by the IFCC. Due to improved sensitivity, they conferred the ability to detect steatosis and significant fibrosis in individuals with dysmetabolism (odds ratio [OR] = 2.31, range 1.40-3.80, P = 0.001; and OR = 3.35, range 1.19-9.42, P = 0.021; respectively), although with a limited accuracy, and significant fibrosis in unselected donors (OR = 2.32, 1.02-5.31, P = 0.045). Updated URLs had a moderate to high accuracy to discriminate liver conditions (area under the receiver operating characteristic curve = 0.81, range 0.78-0.91). Conclusion: Updated URLs by the IFCC method were lower than those calculated in initial studies, but higher than those in use with the recommended old, nonstandardized method, and were able to better predict liver disease. The limited awareness that different techniques are still in use should be regarded as a possible source of medical errors.
Abbreviations

ALT
    alanine aminotransferase
AUROC
    area under the receiver operating characteristic curve
BMI
    body mass index
CI
    confidence interval
HBsAg
    hepatitis B surface antigen
HCV
    hepatitis C virus
IFCC
    International Federation of Clinical Chemistry and Laboratory Medicine
LR
    likelihood ratio
LSM
    liver stiffness measurement
M/F
    males/females
NAFLD
    nonalcoholic fatty liver disease
OR
    odds ratio
URL
    upper reference limit

StephenW

https://aasldpubs.onlinelibrary.wiley.com/doi/10.1002/hep4.1794

StephenW